The long-term objective of this research is to understand at a neurochemical and molecular level the neurotransmitter-neuromodulatory functions of the neuropeptide vasopressin (VP) in the mature and developing brain. Vasopressin containing neurons which originate in the bed nucleus of the stria terminalis (BNST) and medial amygdala (MA) which project to the septum, a structure rich in VP receptors, will be developed as a model system in which to study VP-ergic neurotransmission. The hypotheses to be tested are: 1) that adult septal VP receptors are of the V1-subtype and are coupled to inositol phospholipid (PI) metabolism through interaction with GTP binding proteins, 2) that continuous exposure of VP receptors in adult animals to VP or VP antagonists will induce regulatory changes in these binding sites and in VP-sensitive PI hydrolysis, and that these changes will be different from those observed in similarly treated Brattleboro rats, 3) that exposure of VP receptors to high levels of VP in the early postnatal period will lead to paradoxical "up-regulation" of peripheral and brain receptors, 4) that VP deficiency in developing Brattleboro rats leads to reduced expression of VP receptors in these animals, 5) that transitory VP binding sites which are expressed in the cingulate gyrus, dorsal hippocampus, and caudate nucleus of the rat brain are pharmacologically distinct from those present in adult brain, 6) that gonadal steroids act directly on VP containing neurons of the BNST and MA to regulate expression of the VP gene, 7) that the timing and magnitude of VP gene expression is determined by early postnatal androgen exposure, and 8) that glucocorticoid hormones also regulate VP gene expression in the BNST and MA. To test these hypotheses, a combination of membrane binding, in vitro receptor autoradiography, and in situ hybridization for VP mRNA with computer assisted image analysis will be used. Effects of VP on inositol phospholipid metabolism will be studied in brain tissue slices. Clinical studies have suggested diminished of VP-ergic function is involved in memory impairment in Alzheimer's disease. These studies are essential to understanding the neurotransmitter effects of VP, and in the development of analogs useful in the treatment of cognitive impairment in humans.